One high potency (HP) and two low potency (LP) commercial whole short ragweed (WSR) extracts were assayed for relative potency (RP) by antigen E (AgE-Amb a 1), RAST inhibition, and parallel line bioassay (PLBA). The RP of the HP extract (300 mg AgE) was equal to the reference WSR, but the LP extracts were only about 0.01 of the RP of the reference. Each extract was administered to fall hay fever patients with skin sensitivity to WSR to the maximum tolerated dose, or 0.5 cc of the concentrate, by either a 9- or 40- dose regimen. HP-treated patients had significantly lower symptom scores than untreated controls. No significant difference was noted in the total symptom scores between HP and LP extract-treated patients. Despite approximately 100-fold differences in the RP of HP versus LP extracts, both produced similar frequencies of severe systemic and severe late phase local reactions. When RP of HP and LP extracts were estimated by PLBA, both reached similar peak dosages, similar dosage for IgG WSR antibody response, and comparable IgG WSR antibody levels, indicating that the WSR dose estimates based on RP were bioequivalent. The 9-dose HP regimen produced fewer late phase local and systemic reactions per patient than the 40-dose HP regimen. Most patients experiencing severe systemic reactions were among those most skin sensitive to WSR. The number of systemic reactions per injection was significantly higher at higher WSR doses. One LP extract produced a high incidence of systemic reactions in the initial three injections. With respect to HP, its RP varied approximately 10-fold depending on the skin sensitivity of the patient to heat-stable ragweed allergens, demonstrating that it was compositionally different. However when the dose of this extract was estimated by RP based on the skin sensitivity of each patient, the peak dose of the extract as well as the doses associated with late phase and systemic reactions were found to be similar to the HP doses. This indicated that the immunizing dose estimates of compositionally different WSR extracts based on RP by PLBA were also bioequivalent.